methyl artemisinate | 82869-24-7

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: methyl artemisinate
• 英文别名: methyl 2-[(1R,4R,4aS,8aR)-4,7-dimethyl-1,2,3,4,4a,5,6,8a-octahydronaphthalen-1-yl]prop-2-enoate
• CAS: 82869-24-7
• 化学式: C₁₆H₂₄O₂
• 分子量: 248.365
• InChiKey: AOBAHYLCIGMCHX-UNQGMJICSA-N

物化性质

• 沸点：
  331.0±11.0 °C(Predicted)
• 密度：
  0.973±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  methyl artemisinate 在 tris(1,10-phenanthroline)iron(III) tris(hexafluorophosphate) 、 氧气 、 rose bengal 作用下， 以 乙腈 为溶剂， 反应 6.07h， 生成 methyl <2'S,5'R,6'S>-(E)-<1'-(hydroxymethylenyl)-5'-methyl-6'-(3''-oxobutyl)cyclohex-2'-yl>propenoate
  参考文献：
  名称：

  Copper(II) Trifluoromethanesulfonate-Induced Cleavage Oxygenation of Allylic Hydroperoxides Derived from Qinghao Acid in the Synthesis of Qinghaosu Derivatives: Evidence for the Intermediacy of Enols

  摘要：

  The semisynthesis of qinghaosu (artemisinin) derivatives from qinghao (artemisinic) acid and related compounds is gaining increasing importance despite the fact that the key step in the transformation, the cleavage oxygenation of the intermediate allylic hydroperoxides to form peroxy hemiacetals, is not well understood. It has been found that the allylic hydroperoxide 10 derived from the methyl ester of qinghao acid under catalysis by trifluoromethanesulfonic acid (TfOH) in CH2Cl2 or copper(II) trifluoromethanesulfonate [Cu(OTf)(2)] in MeCN farms a thermally labile intermediate. Chromatographic isolation of the intermediate at low temperature and analysis by low-temperature H-1 and C-13 NMR spectroscopies showed it to be the simple enol 16a, a compound possessing unexpected stability. The enol 16a undergoes autoxidation at room temperature or facile oxygenation at -20 degrees C in the presence of Cu(II) and oxygen to give the peroxy hemiacetal 12. Thus, the catalyzed cleavage of cyclic allylic hydroperoxides proceeds via enol intermediates and it would seem that the propensity for subsequent oxygenation is related to the stability of the enol.

  DOI：

  10.1021/ja00150a009
• 作为产物：
  描述：

  青蒿酸 生成 methyl artemisinate
  参考文献：
  名称：

  BUSTOS, DANIEL A.;JUNG, MANKIL;ELSHLY, HALA N.;MCCHESNEY, JAMES D., HETEROCYCLES, 29,(1989) N2, C. 2273-2277

  摘要：

  DOI：

文献信息

• A short and stereospecific synthesis of (+)-deoxoartemisinin and (−)-deoxodesoxyartemisinin
  作者：Mankil Jung、Xun Li、Daniel A Bustos、Hala N ElSohly、James D McChesney

  DOI：10.1016/s0040-4039(01)93831-6

  日期：1989.1

  The synthesis of (+)-deoxoartemisinin and (−)-deoxodesoxyartemisinin was achieved either from artemisinic acid or from artemisinin.

  （+）-脱氧青蒿素和（-）-脱氧脱氧青蒿素的合成是由青蒿酸或青蒿素实现的。
• Synthesis, Stability, and Antimalarial Activity of New Hydrolytically Stable and Water-Soluble (+)-Deoxoartelinic Acid
  作者：Mankil Jung、Kyunghoon Lee、Howard Kendrick、Brian L. Robinson、Simon L. Croft

  DOI：10.1021/jm020244p

  日期：2002.10.1

  (+)-Deoxoartelinic acid (13), a new hydrolytically stable, water-soluble, and potent non-acetal-type antimalarial drug candidate, was successfully prepared from artemisinic acid by using sulfur ylide and photooxygenative cyclization in seven steps. This compound showed superior in vitro antimalarial activity against the chloroquine-resistant K1 strain of Plasmodium falciparum and higher suppression

  （Y）-脱氧青蒿酸（13）是一种新的水解稳定，水溶性且有效的非乙缩醛类抗疟药物候选物，它是通过使用叶立德硫磺和光氧合环化七个步骤成功地从青蒿酸制备的。该化合物对恶性疟原虫的抗氯喹K1菌株具有优异的体外抗疟活性，并且在体内对沙巴氏疟原虫感染小鼠的抑制作用高于抗关节炎药物（98.7％）。（+）-去氧青蒿酸还显示出显着的稳定性，半衰期为258.66小时，在模拟的胃酸中比临床有用的蒿甲醚稳定23倍，并且溶解度提高，在水中的溶解度比青蒿素高4倍。
• Synthesis and antimalarial activity of (+)-deoxoartemisinin
  作者：Mankil Jung、Xun Li、Daniel A. Bustos、Hala N. ElSohly、James D. McChesney、Wilbur K. Milhous

  DOI：10.1021/jm00167a036

  日期：1990.5

  (+)-Deoxoartemisinin (2), a new and more active antimalarial agent, was successfully prepared from artemisinin in one step using NaBH4 and BF3.Et2O in THF. (-)-Deoxodeoxyartemisinin (5), a potential metabolite of deoxoartemisinin, was also prepared either from 2 or from artemisinic acid. 2 shows 8-fold increased antimalarial activity in vitro against chloroquine-resistant malaria as compared to artemisinin (1). Compound 2 possesses superior in vivo antimalarial activity to 1.

  (+)-去氧青蒿素（2）是一种新型且活性更高的抗疟药物，它由青蒿素（1）通过一锅反应，利用NaBH4和BF3.Et2O在THF中制备而成。(-)-去氧去氧青蒿素（5）作为去氧青蒿素的一种潜在代谢物，既可由2也可由青蒿酸制备。在体外实验中，2对氯喹耐药型疟疾的抗疟活性较青蒿素（1）提高了8倍。在体内，化合物2表现出比1更为优越的抗疟活性。
• Synthesis of New Artemisinin Analogues from Artemisinic Acid Modified at C-3 and C-13 and Their Antimalarial Activity
  作者：Jaehong Han、Jung-Gul Lee、Sun-Sik Min、Si-Hyung Park、Cindy K. Angerhofer、Geoffrey A. Cordell、Soo-Un Kim

  DOI：10.1021/np0101752

  日期：2001.9.1

  eight new artemisinin analogues, including 13-cyanoartemisinin (16), 13-methoxycarbonyl artemisinin (17), 13-methoxyartemisinin (18), 13-ethylsulfonylartemisinin (19), 13-nitromethylartemisinin (20), 13-(1-nitroethyl)artemisinin (21), (3R)-3-hydroxyartemisinin (22), and (3R)-3-acetoxyartemisinin (23). Among the analogues, only compound 20 had antimalarial activity comparable to artemisinin (1).

  青蒿酸 (2) 通过 C-3 处的烯丙基氧化或 C-13 处的共轭加成进行改性，得到 12 甲基青蒿酸酯衍生物 (4-15)。衍生物的光氧化产生了八种新的青蒿素类似物，包括 13-氰基青蒿素 (16)、13-甲氧羰基青蒿素 (17)、13-甲氧基青蒿素 (18)、13-乙基磺酰青蒿素 (19)、13-硝基甲基青蒿素 (130) 1-硝基乙基）青蒿素（21）、（3R）-3-羟基青蒿素（22）和（3R）-3-乙酰氧基青蒿素（23）。在类似物中，只有化合物 20 具有与青蒿素 (1) 相当的抗疟活性。
• Proton and carbon-13 NMR and conformation in solution of some amorphanes (quinghaosu derivatives)
  作者：Anita J. Marsaioli、Fred Y. Fujiwara、Mary Ann Foglio、Nikolai Sharapin、Jin-Sheng Zhang

  DOI：10.1002/mrc.1260321004

  日期：1994.10

  The total proton and carbon‐13 NMR assignments of quinghaosu I, II and V isolated from Artemisia annua cultivated in Brazil and of the synthetic derivatives quinghaosu alkene, ketone and epoxy are reported. The conformations and conformational equilibria of these compounds in solution were obtained from the spectral data and molecular mechanics calculations.

  报道了从巴西种植的青蒿中分离的青蒿素 I、II 和 V 以及合成衍生物青蒿素烯烃、酮和环氧树脂的总质子和碳 13 NMR 归属。这些化合物在溶液中的构象和构象平衡是从光谱数据和分子力学计算中获得的。